Electric-Field-Driven Trion Drift and Funneling in MoSe2 Monolayer.

Excitons, electron-hole pairs in semiconductors, can be utilized as information carriers with a spin or valley degree of freedom. However, manipulation of excitons' motion is challenging because of their charge-neutral characteristic and short recombination lifetimes. Here we demonstrate electric-field-driven drift and funneling of charged excitons (i.e., trions) toward the center of a MoSe2 monolayer. Using a simple bottom-gate device, we control the electric fields in the vicinity of the suspended monolayer, which increases the trion density and pulls down the layer. We observe that locally excited trions are subjected to electric force and, consequently, drift toward the center of the stretched layer. The exerting electric force on the trion is estimated to be 102-104 times stronger than the strain-induced force in the stretched monolayer, leading to the successful observation of trion drift under continuous-wave excitation. Our findings provide a new route for manipulating trions and achieving new types of optoelectronic devices.

Modification of PCNA by ISG15 plays a crucial role in termination of error-prone translesion DNA synthesis.

In response to DNA damage, PCNA is mono-ubiquitinated and triggers translesion DNA synthesis (TLS) by recruiting polymerase-η. However, it remained unknown how error-prone TLS is turned off after DNA lesion bypass to prevent mutagenesis. Here we showed that ISG15 modification (ISGylation) of PCNA plays a key role in TLS termination. Upon UV irradiation, EFP, an ISG15 E3 ligase, bound to mono-ubiquitinated PCNA and promoted its ISGylation. ISGylated PCNA then tethered USP10 for deubiquitination and in turn the release of polymerase-η from PCNA. Eventually, PCNA was deISGylated by UBP43 for reloading of replicative DNA polymerases and resuming normal DNA replication. However, ISGylation-defective Lys-to-Arg mutations in PCNA or knockdown of any of ISG15, EFP, or USP10 led to persistent recruitment of mono-ubiquitinated PCNA and polymerase-η to nuclear foci, causing an increase in mutation frequency. These findings establish a crucial role of PCNA ISGylation in termination of error-prone TLS for preventing excessive mutagenesis.

Modification of ASC1 by UFM1 is crucial for ERα transactivation and breast cancer development.

Biological roles for UFM1, a ubiquitin-like protein, are largely unknown, and therefore we screened for targets of ufmylation. Here we show that ufmylation of the nuclear receptor coactivator ASC1 is a key step for ERα transactivation in response to 17ß-estradiol (E2). In the absence of E2, the UFM1-specific protease UfSP2 was bound to ASC1, which maintains ASC1 in a nonufmylated state. In the presence of E2, ERα bound ASC1 and displaced UfSP2, leading to ASC1 ufmylation. Polyufmylation of ASC1 enhanced association of p300, SRC1, and ASC1 at promoters of ERα target genes. ASC1 overexpression or UfSP2 knockdown promoted ERα-mediated tumor formation in vivo, which could be abrogated by treatment with the anti-breast cancer drug tamoxifen. In contrast, expression of ufmylation-deficient ASC1 mutant or knockdown of the UFM1-activating E1 enzyme UBA5 prevented tumor growth. These findings establish a role for ASC1 ufmylation in breast cancer development by promoting ERα transactivation.

Fabrication and Evaluation of Gellan Gum/Hyaluronic Acid Hydrogel for Retinal Tissue Engineering Biomaterial and the Influence of Substrate Stress Relaxation on Retinal Pigment Epithelial Cells.

Cell therapies for age-related macular degeneration (AMD) treatment have been developed by integrating hydrogel-based biomaterials. Until now, cell activity has been observed only in terms of the modulus of the hydrogel. In addition, cell behavior has only been observed in the 2D environment of the hydrogel and the 3D matrix. As time-dependent stress relaxation is considered a significant mechanical cue for the control of cellular activities, it is important to optimize hydrogels for retinal tissue engineering (TE) by applying this viewpoint. Herein, a gellan Gum (GG)/Hyaluronic acid (HA) hydrogel was fabricated using a facile physical crosslinking method. The physicochemical and mechanical properties were controlled by forming a different composition of GG and HA. The characterization was performed by conducting a mass swelling study, a sol fraction study, a weight loss test, a viscosity test, an injection force study, a compression test, and a stress relaxation analysis. The biological activity of the cells encapsulated in 3D constructs was evaluated by conducting a morphological study, a proliferation test, a live/dead analysis, histology, immunofluorescence staining, and a gene expression study to determine the most appropriate material for retinal TE biomaterial. Hydrogels with moderate amounts of HA showed improved physicochemical and mechanical properties suitable for injection into the retina. Moreover, the time-dependent stress relaxation property of the GG/HA hydrogel was enhanced when the appropriate amount of HA was loaded. In addition, the cellular compatibility of the GG/HA hydrogel in in vitro experiments was significantly improved in the fast-relaxing hydrogel. Overall, these results demonstrate the remarkable potential of GG/HA hydrogel as an injectable hydrogel for retinal TE and the importance of the stress relaxation property when designing retinal TE hydrogels. Therefore, we believe that GG/HA hydrogel is a prospective candidate for retinal TE biomaterial.

The Analysis of Emotion Authenticity Based on Facial Micromovements.

People tend to display fake expressions to conceal their true feelings. False expressions are observable by facial micromovements that occur for less than a second. Systems designed to recognize facial expressions (e.g., social robots, recognition systems for the blind, monitoring systems for drivers) may better understand the user's intent by identifying the authenticity of the expression. The present study investigated the characteristics of real and fake facial expressions of representative emotions (happiness, contentment, anger, and sadness) in a two-dimensional emotion model. Participants viewed a series of visual stimuli designed to induce real or fake emotions and were signaled to produce a facial expression at a set time. From the participant's expression data, feature variables (i.e., the degree and variance of movement, and vibration level) involving the facial micromovements at the onset of the expression were analyzed. The results indicated significant differences in the feature variables between the real and fake expression conditions. The differences varied according to facial regions as a function of emotions. This study provides appraisal criteria for identifying the authenticity of facial expressions that are applicable to future research and the design of emotion recognition systems.

Monolithic Interface Contact Engineering to Boost Optoelectronic Performances of 2D Semiconductor Photovoltaic Heterojunctions.

In optoelectronic devices based on two-dimensional (2D) semiconductor heterojunctions, the efficient charge transport of photogenerated carriers across the interface is a critical factor to determine the device performances. Here, we report an unexplored approach to boost the optoelectronic device performances of the WSe2-MoS2 p-n heterojunctions via the monolithic-oxidation-induced doping and resultant modulation of the interface band alignment. In the proposed device, the atomically thin WOx layer, which is directly formed by layer-by-layer oxidation of WSe2, is used as a charge transport layer for promoting hole extraction. The use of the ultrathin oxide layer significantly enhanced the photoresponsivity of the WSe2-MoS2 p-n junction devices, and the power conversion efficiency increased from 0.7 to 5.0%, maintaining the response time. The enhanced characteristics can be understood by the formation of the low Schottky barrier and favorable interface band alignment, as confirmed by band alignment analyses and first-principle calculations. Our work suggests a new route to achieve interface contact engineering in the heterostructures toward realizing high-performance 2D optoelectronics.

SUMOylation of hnRNP-K is required for p53-mediated cell-cycle arrest in response to DNA damage.

Heterogeneous ribonucleoprotein-K (hnRNP-K) is normally ubiquitinated by HDM2 for proteasome-mediated degradation. Under DNA-damage conditions, hnRNP-K is transiently stabilized and serves as a transcriptional co-activator of p53 for cell-cycle arrest. However, how the stability and function of hnRNP-K is regulated remained unknown. Here, we demonstrated that UV-induced SUMOylation of hnRNP-K prevents its ubiquitination for stabilization. Using SUMOylation-defective mutant and purified SUMOylated hnRNP-K, SUMOylation was shown to reduce hnRNP-K's affinity to HDM2 with an increase in that to p53 for p21-mediated cell-cycle arrest. PIAS3 served as a small ubiquitin-related modifier (SUMO) E3 ligase for hnRNP-K in an ATR-dependent manner. During later periods after UV exposure, however, SENP2 removed SUMO from hnRNP-K for its destabilization and in turn for release from cell-cycle arrest. Consistent with the rise-and-fall of both SUMOylation and stability of hnRNP-K, its ability to interact with PIAS3 was inversely correlated to that with SENP2 during the time course after UV exposure. These findings indicate that SUMO modification plays a crucial role in the control of hnRNP-K's function as a p53 co-activator in response to DNA damage by UV.

Patient-derived neuron model: Capturing age-dependent adult-onset degenerative pathology in Huntington's disease.

MicroRNAs play a crucial role in directly reprogramming (converting) human fibroblasts into neurons. Specifically, miR-9/9* and miR-124 (miR-9/9*-124) display neurogenic and cell fate-switching activities when ectopically expressed in human fibroblasts by erasing fibroblast identity and inducing a pan-neuronal state. These converted neurons maintain the biological age of the starting fibroblasts and thus provide a human neuron-based platform to study cellular properties in aged neurons and model adult-onset neurodegenerative disorders using patient-derived cells. Furthermore, the expression of striatal-enriched transcription factors in conjunction with miR-9/9*-124 guides the identity of medium spiny neurons (MSNs), the primary targets in Huntington's disease (HD). Converted MSNs from HD patient-derived fibroblasts (HD-MSNs) can replicate HD-related phenotypes including neurodegeneration associated with age-related declines in critical cellular functions such as autophagy. Here, we review the role of microRNAs in the direct conversion of patient-derived fibroblasts into MSNs and the practical application of converted HD-MSNs as a model for studying adult-onset neuropathology in HD. We provide valuable insights into age-related, cell-intrinsic changes contributing to neurodegeneration in HD-MSNs. Ultimately, we address a comprehensive understanding of the complex molecular landscape underlying HD pathology, offering potential avenues for therapeutic application.

Ultra-compact exciton polariton modulator based on van der Waals semiconductors.

With the rapid emergence of artificial intelligence (AI) technology and the exponential growth in data generation, there is an increasing demand for high-performance and highly integratable optical modulators. In this work, we present an ultra-compact exciton-polariton Mach-Zehnder (MZ) modulator based on WS2 multilayers. The guided exciton-polariton modes arise in an ultrathin WS2 waveguide due to the strong excitonic resonance. By locally exciting excitons using a modulation laser in one arm of the MZ modulator, we induce changes in the effective refractive index of the polariton mode, resulting in modulation of transmitted intensity. Remarkably, we achieve a maximum modulation of -6.20 dB with an ultra-short modulation length of 2 µm. Our MZ modulator boasts an ultra-compact footprint area of ~30 µm² and a thin thickness of 18 nm. Our findings present new opportunities for the advancement of highly integrated and efficient photonic devices utilizing van der Waals materials.

Longitudinal modeling of human neuronal aging reveals the contribution of the RCAN1-TFEB pathway to Huntington's disease neurodegeneration.

Aging is a common risk factor in neurodegenerative disorders. Investigating neuronal aging in an isogenic background stands to facilitate analysis of the interplay between neuronal aging and neurodegeneration. Here we perform direct neuronal reprogramming of longitudinally collected human fibroblasts to reveal genetic pathways altered at different ages. Comparative transcriptome analysis of longitudinally aged striatal medium spiny neurons (MSNs) in Huntington's disease identified pathways involving RCAN1, a negative regulator of calcineurin. Notably, RCAN1 protein increased with age in reprogrammed MSNs as well as in human postmortem striatum and RCAN1 knockdown rescued patient-derived MSNs of Huntington's disease from degeneration. RCAN1 knockdown enhanced chromatin accessibility of genes involved in longevity and autophagy, mediated through enhanced calcineurin activity, leading to TFEB's nuclear localization by dephosphorylation. Furthermore, G2-115, an analog of glibenclamide with autophagy-enhancing activities, reduced the RCAN1-calcineurin interaction, phenocopying the effect of RCAN1 knockdown. Our results demonstrate that targeting RCAN1 genetically or pharmacologically can increase neuronal resilience in Huntington's disease.

Modeling Huntington disease through microRNA-mediated neuronal reprogramming identifies age-associated autophagy dysfunction driving the onset of neurodegeneration.

Huntington disease (HD) is an inherited neurodegenerative disease with adult-onset clinical symptoms. However, the mechanism by which aging triggers the onset of neurodegeneration in HD patients remains unclear. Modeling the age-dependent progression of HD with striatal medium spiny neurons (MSNs) generated by direct reprogramming of fibroblasts from HD patients at different disease stages identifies age-dependent decline in critical cellular functions such as autophagy/macroautophagy and onset of neurodegeneration. Mechanistically, MSNs derived from symptomatic HD patients (HD-MSNs) are characterized by increased chromatin accessibility proximal to the MIR29B-3p host gene and its upregulation compared to MSNs from younger pre-symptomatic patients. MIR29B-3p in turn targets and represses STAT3 (signal transducer and activator of transcription 3) that controls the biogenesis of autophagosomes, leading to HD-MSN degeneration. Our recent study demonstrates age-associated microRNA (miRNA) and autophagy dysregulation linked to MSN degeneration, and potential approaches for protecting MSNs by enhancing autophagy in HD.Abbreviations: HD: Huntington disease; mHTT: mutant HTT; MIR9/9*-124: MIR9/9* and MIR124; miRNA: microRNA; MSN: medium spiny neuron; STAT3: signal transducer and activator of transcription 3.

Effects of Antimicrobial Administration Route on Growth and Antimicrobial Resistance in Weaned Piglets.

This study aimed to determine how the route of antimicrobial administration affected the growth performance of weaned piglets. Additionally, we aimed to investigate potential differences between antimicrobial resistance developed by antimicrobials administered orally through drinking water, and those administered through feed, in weaned piglets. The research was undertaken on a farm housing 500 sows and involved 150 weaned piglets at 21 days of age. These piglets were evenly distributed into three groups of equal size: water, feed, and control. Antimicrobials were administered through drinking water and feed in the water and feed groups, respectively, while the control group received no antimicrobial treatment. The observation of piglets continued until they reached 70 days of age. The feed conversion ratio in the water group (1.7 ± 0.78) was significantly higher than in the control (2.4 ± 1.77) and feed (2.7 ± 1.68) groups. Additionally, the route of administration did not affect antimicrobial resistance rates. Based on these results, it can be inferred that administering antimicrobials through drinking water is advantageous for pig farming.

Comparative genetic characterisation of third-generation cephalosporin-resistant Escherichia coli isolated from integrated and conventional pig farm in Korea.

OBJECTIVES: Pig-farming systems consist of integrated or conventional farms, and many antimicrobials are used to treat bacterial infections. The objective of this study was to compare characteristics of third-generation cephalosporin resistance and extended-spectrum ß-lactamase (ESBL)/pAmpC ß-lactamase-producing Escherichia coli between integrated and conventional farms. METHODS: Third-generation cephalosporin-resistant E. coli was collected from integrated and conventional pig farms from 2021 to 2022. Polymerase chain reaction and DNA sequencing were performed for the detection of ß-lactamase-encoding genes, molecular analysis, and identification of genetic relationships. To determine the transferability of ß-lactamase genes, conjugation assays were conducted. RESULTS: Antimicrobial resistance rates were higher in conventional farms than in integrated farms; ESBL- and pAmpC-lactamase-producing E. coli rates were higher in conventional farms (9.8%) than in integrated farms (3.4%). Fifty-two (6.5%) isolates produced ESBL/pAmpC ß-lactamase genes. Isolates from integrated farms harboured CTX-15 (3 isolates), CTX-55 (9 isolates), CTX-229 (1 isolate), or CMY-2 (1 isolate) genes; isolates from conventional farms harboured CTX-1 (1 isolate), CTX-14 (6 isolates), CTX-15 (2 isolates), CTX-27 (3 isolates), CTX-55 (14 isolates), CTX-229 (1 isolate), and CMY-2 (11 isolates) genes. Of the 52 ESBL/pAmpC ß-lactamase-producing E. coli isolates, class 1 integrons with 11 different gene cassette arrangements were detected in 39 (75.0%) isolates, and class 2 integrons were detected in 3 isolates. The most common sequence type in both integrated and conventional farms was ST5229, followed by ST101, and then ST10. CONCLUSION: Third-generation cephalosporin-resistant patterns and molecular characteristics differed between integrated and conventional farms. Our findings suggest that continuous monitoring of third-generation cephalosporin resistance on pig farms is necessary to prevent the dissemination of resistant isolates.

Longitudinal modeling of human neuronal aging identifies RCAN1-TFEB pathway contributing to neurodegeneration of Huntington's disease.

Aging is a common risk factor in neurodegenerative disorders and the ability to investigate aging of neurons in an isogenic background would facilitate discovering the interplay between neuronal aging and onset of neurodegeneration. Here, we perform direct neuronal reprogramming of longitudinally collected human fibroblasts to reveal genetic pathways altered at different ages. Comparative transcriptome analysis of longitudinally aged striatal medium spiny neurons (MSNs), a primary neuronal subtype affected in Huntington's disease (HD), identified pathways associated with RCAN1, a negative regulator of calcineurin. Notably, RCAN1 undergoes age-dependent increase at the protein level detected in reprogrammed MSNs as well as in human postmortem striatum. In patient-derived MSNs of adult-onset HD (HD-MSNs), counteracting RCAN1 by gene knockdown (KD) rescued HD-MSNs from degeneration. The protective effect of RCAN1 KD was associated with enhanced chromatin accessibility of genes involved in longevity and autophagy, mediated through enhanced calcineurin activity, which in turn dephosphorylates and promotes nuclear localization of TFEB transcription factor. Furthermore, we reveal that G2-115 compound, an analog of glibenclamide with autophagy-enhancing activities, reduces the RCAN1-Calcineurin interaction, phenocopying the effect of RCAN1 KD. Our results demonstrate that RCAN1 is a potential genetic or pharmacological target whose reduction-of-function increases neuronal resilience to neurodegeneration in HD through chromatin reconfiguration.

Biomimetic sponge using duck's feet derived collagen and hydroxyapatite to promote bone regeneration.

Collagen, a natural biomaterial derived from animal tissues, has attracted the attention of biomedical material researchers because of its excellent cell affinity and low rejection in vivo. In this study, collagen was extracted using livestock by-product flippers, and an experiment was performed to assess its application as a scaffold for bone tissue implantation. For this purpose, we fabricated 2%, and 3% duck's feet derived collagen (DC) sponges. We then compared them to hydroxyapatite (HAp)-coated DC sponges, and measured the porosity and pore size using scanning electron microscopy (SEM) to analyze the physical properties and morphology of DC and DC/HAp sponges. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were carried out to measure the proliferation of bone marrow stem cells (BMSCs) in DC and DC/HAp sponges. An alkaline phosphatase activity assay confirmed the osteogenic differentiation ability of BMSCs. Polymerase chain reaction (PCR) was performed to confirm the BMSC-specific genetic marker. The osteogenic potential was confirmed by the bone formation in an in vivo environment on the scaffold by histological and immunohistochemical analysis. Overall, this study shows that DC/HAp sponges have biocompatibility and good physical properties. Additionally, DC/HAp sponges show potential use as bone graft materials for tissue engineering applications.

Age-related Huntington's disease progression modeled in directly reprogrammed patient-derived striatal neurons highlights impaired autophagy.

Huntington's disease (HD) is an inherited neurodegenerative disorder with adult-onset clinical symptoms, but the mechanism by which aging drives the onset of neurodegeneration in patients with HD remains unclear. In this study we examined striatal medium spiny neurons (MSNs) directly reprogrammed from fibroblasts of patients with HD to model the age-dependent onset of pathology. We found that pronounced neuronal death occurred selectively in reprogrammed MSNs from symptomatic patients with HD (HD-MSNs) compared to MSNs derived from younger, pre-symptomatic patients (pre-HD-MSNs) and control MSNs from age-matched healthy individuals. We observed age-associated alterations in chromatin accessibility between HD-MSNs and pre-HD-MSNs and identified miR-29b-3p, whose age-associated upregulation promotes HD-MSN degeneration by impairing autophagic function through human-specific targeting of the STAT3 3' untranslated region. Reducing miR-29b-3p or chemically promoting autophagy increased the resilience of HD-MSNs against neurodegeneration. Our results demonstrate miRNA upregulation with aging in HD as a detrimental process driving MSN degeneration and potential approaches for enhancing autophagy and resilience of HD-MSNs.

Pluronic F-127/Silk Fibroin for Enhanced Mechanical Property and Sustained Release Drug for Tissue Engineering Biomaterial.

Herein, an injectable thermosensitive hydrogel was developed for a drug and cellular delivery system. The composite was prepared by facile physical mixing of pluronic F-127 (PF) and silk fibroin (SF) in an aqueous solution. The chemical structure, transparency, viscosity, injectability, degradation kinetic, cumulative release of dexamethasone (Dex), a type of corticosteroid drug, and size distribution of the fabricated hydrogels were characterized. Cytotoxicity of the hydrogels was also studied to verify the biocompatibility of the hydrogels. The addition of a proper amount of SF to PF not only improved the mechanical strength but also decreased the degradation rate which improved the fast rate release of hydrophobic drugs. The cytotoxicity of the hydrogel decreased when SF was added to PF in a proper amount. Overall, the results confirm that the composite of PF and SF can be a promising cell and drug delivery system for future application in tissue engineering and regenerative medicine.

Integration of Single-Photon Emitters in 2D Materials with Plasmonic Waveguides at Room Temperature.

Efficient integration of a single-photon emitter with an optical waveguide is essential for quantum integrated circuits. In this study, we integrated a single-photon emitter in a hexagonal boron nitride (h-BN) flake with a Ag plasmonic waveguide and measured its optical properties at room temperature. First, we performed numerical simulations to calculate the efficiency of light coupling from the emitter to the Ag plasmonic waveguide, depending on the position and polarization of the emitter. In the experiment, we placed a Ag nanowire, which acted as the plasmonic waveguide, near the defect of the h-BN, which acted as the single-photon emitter. The position and direction of the nanowire were precisely controlled using a stamping method. Our time-resolved photoluminescence measurement showed that the single-photon emission from the h-BN flake was enhanced to almost twice the intensity as a result of the coupling with the Ag nanowire. We expect these results to pave the way for the practical implementation of on-chip nanoscale quantum plasmonic integrated circuits.

Author Correction: Striatal neurons directly converted from Huntington's disease patient fibroblasts recapitulate age-associated disease phenotypes.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Substrate-directed synthesis of MoS2 nanocrystals with tunable dimensionality and optical properties.

Two-dimensional transition-metal dichalcogenide (TMD) crystals are a versatile platform for optoelectronic, catalytic and quantum device studies. However, the ability to tailor their physical properties through explicit synthetic control of their morphology and dimensionality is a major challenge. Here we demonstrate a gas-phase synthesis method that substantially transforms the structure and dimensionality of TMD crystals without lithography. Synthesis of MoS2 on Si(001) surfaces pre-treated with phosphine yields high-aspect-ratio nanoribbons of uniform width. We systematically control the width of these nanoribbons between 50 and 430 nm by varying the total phosphine dosage during the surface treatment step. Aberration-corrected electron microscopy reveals that the nanoribbons are predominantly 2H phase with zig-zag edges and an edge quality that is comparable to, or better than, that of graphene and TMD nanoribbons prepared through conventional top-down processing. Owing to their restricted dimensionality, the nominally one-dimensional MoS2 nanocrystals exhibit photoluminescence 50 meV higher in energy than that from two-dimensional MoS2 crystals. Moreover, this emission is precisely tunable through synthetic control of crystal width. Directed crystal growth on designer substrates has the potential to enable the preparation of low-dimensional materials with prescribed morphologies and tunable or emergent optoelectronic properties.